Methadone and QTc prolongation (Letter to the Editor)

Original article: Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368;9535;556-557

Byrne and Stimmel response: Byrne A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366 (below first item)

Authors� response: Mehler PS, Krantz MJ. Authors� reply. Methadone and QTc prolongation. Lancet 2007 369:366-7 (below second item)

Methadone and QTc prolongation.

Mori Krantz and Philip Mehler (Aug 12, p 556)1 write about preventable cardiac risks of methadone treatment. They state: �In 1973, clinicians in New York sought an explanation for a perceived increase in the risk of sudden death in heroin addicts, even in those successfully treated with methadone�.2

We have re-read this reference (one of us, BS, was co-author) and find no reference to unexplained deaths in methadone patients. Of more importance, however, is that the patients in the methadone group were all using several other drugs in addition to heroin for at least 3 days before the cardiography. There was no group in that study that was only using methadone. The frequency of QTc prolongation was 18% in those using heroin versus 34% in those misusing several drugs while on methadone maintenance. We could find no other series of unexplained deaths of addicts in treatment at that time, nor in the decades since.

After widespread use throughout the world, often under close medical supervision, it is hard to accept that a serious side-effect would be entirely overlooked. Most of the small number of reported torsades cases have involved other risk factors or doses averaging nearly 400 mg daily for pain management 3 - ie, more than four times the average used in addiction treatment.

Krantz and Mehler�s implication that high doses of methadone should be avoided could paradoxically lead to more cocaine use and other highrisk behaviour, far outweighing any possible cardiac side-effect. 4

It seems more reasonable to monitor the changes in QT intervals when the need for high doses arises, especially in circumstances where multiple drugs are needed to control pain, depression, or other complex disorders.

We declare that we have no conflict of interest. *Andrew Byrne, Barry Stimmel

1 Krantz MJ, Mehler PS. QTc prolongation: methadone�s effi cacy-safety paradox. Lancet 2006; 368: 556�57.

2 Lipski J, Stimmel B, Donoso E. The effect of heroin and multiple drug abuse on the electrocardiogram. Am Heart J 1973; 86:663�68

3 Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med 2002; 137: 501�04.

4 Borg L, Broe DM, Ho A, Kreek MJ. Cocaine abuse sharply reduced in an effective methadone maintenance program. J Addictive Dis 1999; 18: 63�75

Authors� reply:

We thank Andrew Byrne and Barry Stimmel for their insightful comments. However, we stand by our contention that sudden death is not a rarity among heroin addicts, whether treated with methadone or not. Therefore, we feel this is worthy of further investigation, given a report of rising mortality attributed to methadone.1

Regarding the 1973 study by Lipski and Stimmel, 2 we agree that there is a confounding effect of poly-drug abuse on the QTc interval that cannot be adjudicated in a post-hoc review of this study. Nonetheless, the fact that clinically important QTc prolongation was nearly twice as common among patients receiving methadone (proven by urine toxicology) than those who were methadone-naive is uncanny.

We concur with Byrne and Stimmel that electrocardiographic monitoring seems most appropriate for patients in whom the methadone dose is being escalated and among those on multiple QTc-prolonging drugs. Moreover, we also wholeheartedly agree that highdose methadone is very effective in reducing illicit drug use. However, we believe that a high-dose methadone strategy has a clear safety trade-off. Our field has moved dramatically towards higher methadone doses over the past decade. In our methadone maintenance treatment practice in Denver, CO, USA, 30�60 mg/day is an infrequently prescribed dose, whereas doses over 100 mg/day are now the norm.

It is with consternation that we acknowledge the escalation of dosing standards as our best explanation for the increase in morbidity and mortality among methadone-treated patients. Indeed, these very concerns regarding high-dose methadone are expressed by the manufacturer in a just-released black box warning label.3

We declare that we have no conflict of interest.

*Philip Mehler, Mori Krantz

Denver Health Medical Center, Denver, CO 80204, USA

1 Ballesteros MF, Budnitz DS, Sanford CP, Gilchrist J, Agyekum GA, Butts J. Increase in deaths due to methadone in North Carolina. JAMA 2003; 290: 40

2 Lipski J, Stimmel B, Donoso E. The effect of heroin and multiple drug abuse on the electrocardiogram. Am Heart J 1973; 86:663�68

3 Roxane Laboratories Inc. Dolophine hydrochloride.

Amphetamine / Stimulant Use: Presentations, complications, interventions

30/01/2007

Speakers: Dr Alex Wodak, Director of the Alcohol and Drug Service, and Ms Tarra Adam, Stimulant Treatment Program, Clinical Program Manager, St Vincent�s Hospital, Darlinghurst. Chaired by Dr Bob Batey.

Summary written by Judith Meldrum and Richard Hallinan.

Dr Wodak gave an overview of increasing amphetamine use around the world. In 2002, of 91 countries, 56 showed increasing "abuse" of amphetamines, and 11 showed a decrease. There was an increase in amphetamine labs in the years from 1998 to 2004 of 300 to 18,000, with production of Amphetamine Type Substances (ATS) rising from 312 tons to 480 (UNODCCP Global Illicit Drug Trends 2002). Among 15-64 year olds in 2006 there was a prevalence of ATS use in Asia of 0.6%, Oceania of 3%, and Global 0.6% (UNDCP 2006 World Drug Report).

Australian Institute of Health and Welfare statistics show an increase in admissions for amphetamine-related psychosis, from approximately 1000 in 1999/2000 to approximately 1600 in 2003/2004. There has probably been a further increase since then, however the increases have been patchy across the country, with increases in NSW and Victoria being less than other states (a large increase in the year 1999 can be attributed to the change from ICD 9 to ICD 10 definitions).

Recently there has been a trend away from plant based substances to chemical based drugs due to efforts to avoid both the vagaries of weather, and improved surveillance by air and satellite.

To get an idea of the size of the problem in economic terms Dr Wodak pointed out that the size of the illicit "drug industry" in the UK was about the same as British Airways.

Regarding the cost effectiveness of treatment, there have not been any studies specifically looking at amphetamines but it is more cost effective to spend money on cocaine drug treatment than on drug law enforcement (Rydell, Everingham. Controlling Cocaine: Supply Versus Demand Programs, RAND, 1994.) Because of similarities to cocaine, these conclusions may be also relevant to amphetamines.

In the words of the economist Milton Friedman: "So long as large sums of money are involved - and they are bound to be if drugs are illegal - it is literally hopeless to expect to end the traffic or even to reduce seriously its scope. In drugs, as in other areas, persuasion and example are likely to be far more effective than the use of force to shape others in our image."

Dr Wodak described typical presentations of amphetamine use: a psychosis that looks like schizophrenia; severe, even suicidal, depression; aggressive behaviour; strokes, hypertension, and arrhythmias; possibly risky sex including HIV risk; infections from injecting drug use including HCV, septicaemia, bacterial endocarditis; and general "social catastrophes" - financial problems, lost jobs and broken relationships, and gambling problems.

No specific regimen has been found to be better or worse than any other for withdrawal management, as amphetamine withdrawal is not well understood.

Cochrane reviews have found evidence about the treatment for amphetamine psychosis is limited: medications of interest are conventional antipsychotics, newer antipsychotics and benzodiazepines. An injection of "anti-psychotic drugs can help relieve the symptoms of amphetamine psychosis within an hour, but there is not enough evidence to show what can help after that".

Among psychosocial interventions for amphetamine dependence, motivational interviewing and cognitive behavioural therapy show promise. Most in the audience had not used the excellent recommended handbook by Baker, Kay-Lambkin, Lee, Claire and Jenner. �A Brief Cognitive Behavioural Intervention for Regular Amphetamine Users� Department of Health and Ageing 2003
Among non-agonist pharmacological treatments for amphetamine dependence, 30-40 different drugs have been evaluated but none really found to be helpful (see Cochrane Review).

Setting the context for agonist pharmacological treatments, Dr Wodak gave the following overview: some amphetamine, especially methamphetamine, users become very chaotic, very volatile, and some become violent. As they may develop paranoia or psychosis, so engaging patients often takes longer, and may be much harder than with other substance dependent patients. They need access to prompt, effective mental health support, and most respond very positively to psychosocial interventions. However a few people with severe intractable use may need Amphetamine Substitution Treatment (AST) in combination with psychosocial interventions.

We were pointed to two reviews of the numerous studies of Amphetamine Substitution Treatment (dating from Griffith Edward�s first study in the 1960s, which gave negative results).

Shearer J, Sherman J, Wodak A, van Beek I. Substitution therapy for amphetamine users. Drug and Alcohol Review 2002; 21 (2), 179-185.

Grabowski J, Shearer J, Merrill J, Negus S. Agonist-like replacement pharmacotherapy for stimulant abuse and dependence. Addictive Behaviors. 29 (2004); 1439-1464.

These reviews show that, comparable to the situation for methadone in the 1970s, there is reasonable evidence for the effectiveness and safety of AST. It may be not needed for as high a percentage, nor as long, as for heroin dependent people who need methadone.

Dr Wodak reminded us of the principles of drug substitution treatment:

1. to replace: a short acting drug with a longer action one; an illegal drug with a legal drug; an injectable drug with an oral drug; and

2. to stabilise, counsel, and then where ever possible wean off, as in nicotine replacement, and opioid substitution treatment.

The NSW Department of Health established Stimulant Treatment Programmes in November 2006 at St Vincent�s Hospital, Darlinghurst and in the Hunter New England region. These programmes offer psychosocial interventions but for severe and refractory cases which meet strict criteria, trials are using immediate release dexamphetamine, as slow release amphetamine (which would be preferable) is not yet licensed for use in Australia. There will be daily supervised dosing of 60mg maximum, only for people with severe intractable problems, with small numbers of about 30 per year in each centre. The programmes are being independently evaluated.

The selection criteria are very strict, as Dr Wodak believes it is wiser to start such a treatment with strict limits and later liberalise it if appropriate, rather than "let the genie out of the bottle" too soon.

The power of substitution treatment has been shown in Zurich, where there has been saturation treatment with methadone and other opioids (including prescribed heroin), accompanied by a marked decrease in heroin use, drug overdose, crime and heroin seizures by police, and an 82% reduction in new heroin users from 850 in 1990 to only 150 in 2002. (Nordt, Stohler. Lancet 2006 367 1830-34).

Another benefit may be if ATS acts like a carrot, getting people with problems to ask for help. A number of people on the waiting list for ATS at St Vincent�s Hospital have improved just with psychosocial interventions while being considered for pharmacotherapy.

Tarra Adam then spoke on her work with amphetamine users at Sydney�s St Vincent�s Hospital. She sees those that present at the hospital with problems related to amphetamine use, or who refer themselves.

Some present with aggression or violence which is out of character and worries them. Many have learnt to manage their use reasonably well, before seeking any treatment.

There is a perception that Alcohol and Drug Services are not for them, and historically these services may have had little to offer. ATS users are often suspicious of the service and whether the service can meet their needs, and may appear to be testing out the therapists, having a strong sense of what they want. Often they wish to be seen in a different area or using a separate entrance, because they are "not like the others".

Amphetamine users do tend to show a different profile, being less impoverished and more educated, motivated but hard to engage, often successful at work with a wide range of social contacts, and in better social circumstances than heroin users. Most are daily users, some injecting 3 times a day, some up to 9 times. The majority of people seen at the St Vincent�s Hospital Stimulant Treatment Program are smoking "crystal". Not many switch between amphetamines and cocaine.

A range of therapies is offered, including Motivational Interviewing, Cognitive Behavioural Therapy, and people may be referred to a �SMART Recovery� group. However CBT may be just too difficult for a person who is chaotic or paranoid, and often experience cognitive impairment during periods of use or whilst in withdrawal. In the early stages of treatment, some people find it difficult to concentrate and connect with how their thoughts and feelings influence their behaviour. In addition, talking about triggers and motivations to change with stimulant users has in our experience, increased people�s craving for the drug and can contribute to ongoing use and/ or relapse. Therefore we concentrate on addressing the wider impact of stimulant use on their sense of self, the impact of use on their relationships, rather than concentrating on the drug use itself.

Therefore, other approaches may be needed, with the aim of trying to engage the person.

Narrative Therapy is an example: here the emphasis is centred on people as the experts in their own lives. It views problems as separate from the person and holds that people come with many skills, beliefs, values and abilities that will assist them to reduce the influence of problems such as stimulants in their lives. People often present to therapy with a problem saturated story that dominates beliefs about themselves and influences the choices they make. Narrative conversations seek out the alternative/ preferred stories �stories that are identified by the person about how they would like to live their lives, what it would mean to them to make these changes and supports them to perform this meaning. The therapist seeks out examples of such stories in their lives which support people to break from the influence of the problems they are facing and create new possibilities for their future by increasing awareness of their skills, beliefs, values, and abilities to reduce the influence of stimulants in their lives. A reference for those interested to know more is "What is Narrative Therapy?" by Alice Morgan (can be ordered from the Dulwich Centre - the link for a summary of her book is: http://www.dulwichcentre.com.au/alicearticle.html)

In the second half, chaired by Dr Bob Batey, a range of case vignettes was discussed.

The first case was a woman who declared "I always shoot speed on my pension day, Doc. It is the only time I ever clean the house � but now all my veins are gone!"

Among the points raised were: possible causes of the exhaustion include following a binge, chronic hepatitis C, and depression. A question was raised about the safety of using antidepressants, including SSRIs, in people who use stimulants, including MDMA. Although this was a theoretical risk, given that these medications and drugs raise monoamine levels in synapses, the expected "epidemic of Serotonin Syndrome has not materialised", as one participant put it. It may be worth suggesting safer ways of administration, as a harm reduction measure, and may be appropriate to refer her for financial management assistance through Centrelink, which offers the Centrepay service for regular payments. It was generally agreed that she was not suitable for AST, given the intermittent nature of her use.

In the second case, a man announced "After I use crystal meth I turn into somebody else. I thought I knew how to fly and jumped off the balcony two storeys up to save using the stairs. Now I�m in plaster with two fractured heels and I can�t even get up those stairs".

Problems like this occur especially with use of other substances as well, such as benzodiazepines, and often end up in jail, or hospital. Once the person settles they may be able to look at their substance use, especially if they are laid up in hospital. An important question is how worried friends or family can help decrease the risk of harms like this: one response is that health professionals need to help "significant others" who seek help in the first instance by helping them look after themselves.

This was also true for the following case, where flatmates sought advice about a young man who had moved in recently from Darlinghurst where "it was too easy to go out every night". He regularly used "ecstasy", took Ritalin for ADD, also selegiline which he read on a web site was good for ADD. He was often up all night, constantly reorganising his room with his things strewn all over the yard. One day he declared angrily "I know you�ve been in my room snooping around. You let things slip that show that you did it. I wish I had video surveillance up there".

Tarra Adam said this was a typical presentation to the Alcohol and Drug Service at St. Vincent's Hospital, except that usually the person absolutely believes that others were doing the video surveillance.

A comment was that nothing could be taken at face value in this case: neither the ADD diagnosis, the precise substances used, nor any other psychiatric diagnosis.

In the next case, a 32 yo man, injecting ATS for 2 years, said: "I'm using ice every day and I can't pull up. Can you give me something to help me detox? Or can I go to a detox somewhere?" Even though the evidence about the amphetamine withdrawal syndrome is limited and there seems to be little benefit from medications, many "detox" facilities will admit amphetamine users. One rehab allows the person to sleep and then clean up, maintaining good hydrations being very important. As many ATS users prefer benzodiazepines to manage their withdrawal, a case could be made in community practice for dispensing a small amount of diazepam to encourage engagement with treatment in future.

The final case was a 34 yo man on MMT for 7 years, 11 years injecting, probably 10 years chronic HCV with fluctuating elevated ALT. His methadone dose was 110 mg and his total testosterone was 5.0 -7.2 mmol/L on repeated (morning) testing. He continued to inject ATS several times a week throughout MMT, saying otherwise he has no energy. He was little motivated to change his ATS use.

The reasons for this man's lack of energy could include hypogonadism (probably from opioids), chronic hepatitis C, depression, or the effect of amphetamines themselves. Among the approaches could be a trial of methadone reductions or androgen replacement (chronic viral hepatitis is not a contraindication for use of testosterone and its esters, which should be used in preference to synthetic androgens). One could offer antiviral treatment for hepatitis C, which may be a motivation to stop injecting drug use (injecting should not be a contraindication for hepatitis C treatment). a trial of antidepressants may be indicated. These strategies should probably be tried serially rather than simultaneously, to avoid diagnostic confusion in the event of an improvement in energy.

Physicians in opera

BMJ 2006 333;1333-1335

Willich N. Physicians in opera - reflection of medical history and public perception

Dear Colleagues,

There is an amusing piece in the festive issue of the world's oldest medical journal.

It seems that on balance we doctors are a despicable lot as represented in opera . with a few nice but largely impotent exceptions (the soprano always dies in the end!).

Full paper Physicians in opera - reflection of medical history and public perception 572k pdf - opens in new window.

"Merry Christmas" to listers who may celebrate that sort of thing - there are few enough in Australia where we (lapsed poveri) generally worship sun and sand at this time of year!

Andrew Byrne ..

Morphine versus methadone: a crossover comparison.

Slow release oral morphine versus methadone: a crossover comparison of
patient outcomes and acceptability as maintenance pharmacotherapies for
opioid dependence. Mitchell TB, While JM, Somogyi AA, Bochner F. Addiction
(2004) 99: 940-945

Dear Colleagues,

This study took 18 consenting methadone maintenance (MMT) patients and
transferred their treatment to once daily, supervised slow-release oral
morphine. They then reported up to 8 weeks progress and return to
methadone. Fifteen managed the transfer without difficulty, three returning
to MMT prematurely. Reports of symptoms, side effects and preferences over
up to six weeks in the 15 were positive, about three quarters preferring the
morphine tablets, only one in five preferring the original methadone. While
this is not scientific proof of a superior treatment, it is certainly an
indication that morphine can be an acceptable alternative for most MMT
patients, with certain reported benefits in a proportion of them.

The initial conversion ratio used was 3.5:1 but every single patient
required increased doses for withdrawal symptoms, up to an average of 4.6:1
. thus, for example, a patient on 100mg of methadone might need up to 460mg
of morphine. At least two of the 11 cases (18%) returned to MMT on higher
doses (45 to 50 and 120 to 130). One of these, interestingly, was already
on the maximum dose according to the range quoted (25-120mg daily), but
evidently needed still more on medical review when returning to methadone.

The mean methadone dose in this Adelaide trial at 78mg daily is higher than
previous reports. However, it is likely that the optimal mean dose is yet
to be reached, although increases are happening slowly elsewhere (D'Aunno et
al). Until the mean dose of methadone is nearer 100mg (like Dole's very
first report) it is probable in my view that a proportion of patients will
suffer, simply by being prescribed inadequate doses. The lowest doses
overall may be in England and Victoria (Aust) where one finds poor quality
maintenance treatment along with either too much supervision (Victoria) or
too little, as in the UK. New South Wales also has many treatment
deficiencies, most glaring being a lack of treatment services in high risk
areas such as the Hunter Valley, South-western and inner Sydney. There are
also unreasonable restrictions and a lack of flexibility in some aspects of
management, especially with buprenorphine.

I understand that in NSW, morphine has been approved for over 100 patients
who have been previously registered as dependency cases. The approvals are
mostly for slow release oral morphine for 'pain management', often after
motor accidents, infections or skin grafts following overdoses. Supervision
of doses is not always compulsory. It is not usually possible to completely
separate an individual requirement for opiates for (1) dependency or (2)
analgesia purposes . and it may not matter, except for some legal aspects.

This study from Adelaide adds further evidence that a wider variety of
opioids can be safe and effective in dependency situations and the old view
of 'methadone for dependency and morphine for pain' is dated and arbitrary.
Thus we now need to find out if we can improve on 'trial and error' to
determine optimal management for our patients using methadone, buprenorphine
or alternative oral or even parenteral opioids in pharmacotherapy for
dependence.

Congratulations to Addiction for showcasing this seminal study as the lead
article for the month. Note this study followed a rigorous report by the
same authors on morphine's pharmacokinetics (see below). The first such
report I can find is from Dr Sherman in Melbourne, followed by Whitton et al
in Sydney (both 1996).

Refs: Mitchell TB, White JM, Somogyi AA, Bochner F. Comparative
pharmacodynamics and pharmacokinetics of methadone and slow-release oral
morphine for maintenance treatment of opioid dependence. Drug Alc Depend
(2003) 72;1:85-94]

Whitton G, Sunjic S, Webster I, Wickes W. Use of morphine mixture to
stabilize opiate dependence. 1996 Drug Alc Review 15: 427
Sherman JP. Managing heroin addiction with a long-acting morphine product
(Kapanol). Med J Aust 1996:165;239

Comments by Andrew Byrne ..

APSAD Conference - day three. Nov 8 2006 and various observations

APSAD Annual Scientific Conference. Cairns, Queensland.

Wed 8th November 2006.

This year�s conference was held in a purpose built conference centre, two to four city blocks from the main hotels. This had some good and bad points. Personally, I found it awkward but the walk probably did me good. The venue was comfortable if somewhat sterile - it was rather like being in an airport, without the exotic destinations. The conference rooms all had purpose built power-point connections controlled simply by the use of a mouse on the lectern which was ideal once one got the hang of it. Everything was electronically signposted and sessions timed down to the minute.

All credit to Professor Peter D'Abbs and his committee of locals who did a splendid job without the benefits of the mighty workforce available in the major capitals.

This year, there was no further debate on the contentious heroin �shortage� dating from December 2000. However, Lisa Maher did a noble job of trying to tease out the changes regarding hepatitis C seroconversions among injectors recruited from three city sites including outreach services. She found dramatic reductions (~50%) in heroin use and corresponding increases in cocaine use with higher risk taking behaviours after December 2000. There was a trend to higher rates of hepatitis C following the change in heroin availability.

On the same subject, in a letter to this month�s Addiction journal, Degenhardt and Hall back away from ascribing law enforcement as a major factor in Australia�s heroin shortage in 2001, based on Canadian evidence of �massive decreases in three markers of heroin use� there concurrently (Wood, 2006). While Degenhardt and Hall now state that supply reduction from producer countries may have played a larger role, they still do not address competition from Chinese markets (see below for evidence of the popularity of opiates in that country) and cling tenuously to their thesis: "... that the Australian heroin shortage may have been one of those rare occasions in which law enforcement activities contributed to reduced drug supply."

Aside from recent research, Maher, Hall and Degenhardt may learn more about the heroin shortage�s origin by reading William Burrough�s classic short story "The Junky�s Christmas".

We commenced the third a final day of the conference with a witty talk by David Crosbie on the ins and outs of alcohol policy: what can and cannot be done, as well as some things which ought to be done but probably won�t be. Professor Norman Giesbrecht then gave a perspective from Canada on a variety of community based initiatives. He pointed out that when following proven strategies with a sound design they were likely to be effective. However his final observation was that vast harm can be avoided by major policy shifts, dwarfing the effect of the smaller community based �boutique� projects. However, the latter can sometimes give direction for the larger policy shifts.

Dr Aramrattana gave us the discomforting news from Thailand that a �war on drugs� in 2003 involved a couple of dozen deaths officially but possibly hundreds (or even thousands) more unofficially. There were 200,000 drug users given compulsory treatment at that time of whom 1500 were surveyed with rather rosie sounding results. He seemed to have mixed messages and perhaps this reflects what is happening on the ground. It would appear that despite this draconian policy, Thailand still has a substantial drug problem.

Next we had a series of six more parallel presentations and workshops. Dr Mark Hardy, GP from Sydney�s St George area, did a fine job of demonstrating how new Medicare item numbers for Enhanced Primary Care (EPC) suit chronic conditions and ensure that doctors who treat addicted patients should be better recompensed than ever before. He felt that there is still under-utilisation of Health Care Plans, Team Care Arrangements, Case Conferences, Home Medicines Reviews and the like (see new mental health items). In some states, pharmacotherapy patients sign a treatment agreement which enshrines a goal of 3-monthly comprehensive multidisciplinary case management which is covered by two current Medicare items, initial and follow-up (between them, over $200 rebate). There is a pharmacist, practice nurse and prescriber at the minimum and most patients have other carers (eg. hepatologist, psychiatrist, physiotherapist, dentist, etc).

The next conference strand most importantly brought us up to date with China and its belated but monumental and pragmatic moves to address opiate addiction using hundreds of methadone clinics (195 are due to open in 2007). Dr Zhang Ruimin from Yunnan province was unable to attend but his presentation was given by Dr Nick Walsh quoting over 1000 health care workers with detailed education in pharmacotherapies [see my story on the first methadone clinic in Beijing just one year ago]. It is not all good news as drug use, prison and compulsory detoxification were outlined from China, Vietnam and Indonesia by other speakers.

Other sessions were held on policing, policy and problems in the indigenous community, including a description of NSW Monaro region�s opiate and stimulant approaches. The afternoon sessions covered party drugs, injecting complications, consumer perspectives, youth and "future challenges".

I was told that on the Wednesday afternoon John Strang from London gave a witty talk to RACP Addiction Chapter members taking off Donald Rumsfeld: "There are things we know that we know, and things that we know we don't know ... ". It is a shame that Strang still does not directly address the public health disaster he so clearly describes from England regarding pharmacotherapies. Furthermore, he might propose some way out of the mire which has led to some of the worst drug statistics in the European Union.

There were various �add-ons� to this conference such as a Sunday afternoon detailing session sponsored by Reckitt Benckiser, culminating in a panel �Hypothetical� to focus on expansion of treatment and changing the paradigm "unsupervised treatment" hosted by Dr Norman Swan of the ABC. There was also a separate �drug trends� meeting on the Sunday with Chapter, APSAD general and council meetings as well as a �wind-down� on the Wednesday evening.

Comments by Andrew Byrne ..

Reference:

Wood E, Stoltz J-A, Li K, Montaner JSG, Kerr T. Changes in Canadian heroin supply coinciding with the Australian heroin shortage. Addiction 2006 101:689-695

Dependency issues in gaols, juvenile justice and drug courts

21 November 2006

Dr Gilbert Whitton began by giving us an overview of the prison population in Australia, currently at 24,000 and rising by 5% per year, 50% of prisoners being recidivist and 20% aboriginal. Based on the 2001 Inmate Health Survey, there are high rates of intellectual disability, and mental illness especially depression. Histories of sexual abuse and of head injury are common. Specific figures are not available for ADHD or personality disorders in NSW prisons, but these are prevalent as are substance use disorders. Eighty percent of prisoners are smokers (though 80% of them report that they are interested in stopping); one third of women and half of men have used alcohol at hazardous levels. Cannabis is the most common illicit substance of dependence, followed by amphetamines and then heroin. Hepatitis C prevalence rose from 34% to 40% between 1996 and 2001.

Among police detainees, 20% are affected by amphetamines, 20% by benzodiazepines and 10% by heroin at the time of arrest. Three quarters of prison sentences are linked to drugs in some way, and 60% had offended while under the influence of drugs and/or alcohol.

Between arrest and reaching the facilities of the Department of Correctional Services (after sentencing or on remand) the responsibility for a prisoner's health rests with the NSW Police. This applies in the holding cells of a police station, court cells (such as Sydney Central Court or in the Sydney Police Centre).

Justice Health is actually part of the NSW Health Department, not the Department of Correctional Services. A prisoner's medical records are therefore protected by the same confidentiality provisions as any one else's, and do not form a part of the prison records.

Seven percent of the methadone population in NSW are in prison at any one time, though the turnover is higher, about 100/month. The risk of overdose is much higher on release from prison: 15 times higher if the person is released not on MMT, three times higher if released on MMT. Unfortunately, the Department of Correctional Services cannot offer methadone or buprenorphine at every prison in NSW, often for logistical reasons such as the legal requirement need to have two people present for dosing, one of whom must be a nurse.

The Department of Juvenile Justice has its counterpart in Adolescent Health, part of Justice Health. Dr Whitton described the increasing activities of the Adolescent Health service, covering smoking is a high priority. There is a black market in cigarettes as these are prohibited in Juvenile Justice facilities. Methadone or buprenorphine treatment requires a second medical opinion for those under 18 years.

An old saw about people in prisons is: "If the drugs came before the crime, there is hope, but if the crime came first there's little hope". Dr Whitton gave evidence of very early histories of alcohol and cannabis use in the teenage prison population.

Sue Jefferies, who previously worked in the prison medical service joined the Drug Court in 1999. She informed us of how Drug Court operates under the Drug Court Act which allows convicted offenders to be diverted into programmes to reduce substance dependency and related crime. The aims are to reduce incarceration and the need to use substances, and to increase involvement in treatment.

Eligibility criteria are:

1. DSM IV for opioid dependency.

2. a prison sentence must be likely.

3. non violent crimes only considered.

4. if there is a previous history of violence, especially driving related, a risk assessment is required.

5. the person must live in a designated area - currently western Sydney.

6. no current serious mental illness.

A typical programme involves parole, attendance at groups, counselling, substitution treatment, for a minimum of a year.

People can be breached for non-compliance, being sent back to prison for a period of time - for practical reasons a 3 day spell may be stored up and added to other 'penalities' all to be served in one episode. Urine toxicology is performed 3 times a week. Actual titres of cannabinoids are used, and in consultation with a toxicologist conclusions are drawn about recent cannabis use. Some leniency is shown at first, but abstinence may be required. This fascinating area of differential or quantitative urine toxicology will be looked at in a Concord seminar next year.

Since 1999 there have been 1200 people inrolled in the programme. There are 270 out of prison having completed the programme successfully, and another 370 returned to serve their sentence.

The Drug Court is distinct from the MERIT programme, which is a pre-sentence programme for 'bailable' offences, administered by parole officers. It is a 3 month programme, but the same principles are used, including participation in groups, counselling and goals monitored by strict urine testing.

Health professionals do not refer people to the Drug Court, but Sue Jefferies is keen that GPs and addiction specialists are involved to ensure a smooth transition at the end of the programme.

A compulsory drug treatment programme has also commenced in NSW.

Several case studies were presented in the second half:

A seventeen year old was given symptomatic withdrawal management and eventually started on methadone. The rate of induction reflected both the need for a safe protocol which the doctor may have to write up without medical review being feasible for a week or two, and the low risk of illicit opiate access in prison. A sad observation was that this person was arrested after spending many weeks trying unsuccessfully to get onto buprenorphine maintenance. With early treatment perhaps he could have been kept out of gaol.

The case entitled "I had a liver autopsy in gaol but they stopped the interferon, dunno why" raised the question about how to get medical records (such as liver biopsy and hepatitis treatment results) from a person's time in prison. Stephanie Smith, Public Health Nurse at Mulawa Correctional Centre and a regular Concord participant, advised us of the contact numbers to obtain medical records of people released from custody: Phone 9289 5011/5012/5013; Fax 9289 5014. "It usually takes a few days for the files to get to records, which is located at Silverwater, so if they are recently released you are best off contacting the clinic directly."

"I don't want to go to gaol, they'll make me the pretty boy for sure". The issue of male rape in prison is a real one. Apparently one judge responded to a pre-sentence plea for the risk of rape to be considered with the comment: "Show me the evidence" (books and official reports have since been written on the subject). We heard about an ex-prisoner's advice to threats of rape when arriving in prison. A young cell-mate who had yelled out defiantly in response to threats of rape was the only one who got targeted. The usual advice is "keep your mouth shut". Many rapists are actually homophobic, and the rape is all about power.

Men who have been raped are often afraid or ashamed to report it. They may present to the clinic with complaints about their bowels instead.

"In gaol they used to punch me in the gut to spew my methadone so they could shoot it up". We were advised that this sort of thing is quite real. Another graphic example of the need to 'get stoned' in prison: woman may strap a tampon to their back of teeth and swallow it before dosing to absorb the methadone from the stomach. The product can be filtered through a kitchen scour. Diversion of buprenorphine is likewise a big problem, and sometimes requires a transfer to methadone.

One question showed some ignorance about typical prison conditions: Do people get a cell to themselves? The answer given was a definite "NO".

Summary compiled by Gilbert Whitton, Sue Jefferies and Richard Hallinan.

Sent from Byrne Surgery http://www.redfernclinic.com/

Next year's program is being finalised presently. It will start with a talk on stimulant problems by Dr Alex Wodak of St Vincent's Hospital on Tuesday Jan 30th 2007.

Cairns APSAD Conference 2006 summary: day two

APSAD Annual Scientific Conference. Cairns, Queensland.

Tues 7th November 2006.

The day started with a spirited talk by Shane Kawenata Bradbrook on tobacco use from a Maori perspective. His �Maori Smokefree Coalition� had a major input into a global treaty to address the epidemic, winning a number of international legal cases in which tobacco had been promoted using grossly inappropriate means. He spoke logically and passionately about the desire to rid his country of tobacco, reminding us that his people (and other non-American indigenous people) had always lived without tobacco before European colonisation.

Next we had a presentation from veteran criminologist and researcher Don Weatherburn from NSW. He outlined the alarming figures which were presented at the first �Deaths in Custody� report 15 years ago and showed that most have become even worse since, despite enormous efforts and expenditure at federal and state levels. He reminded us that the indigenous community is over-represented 10 fold or more in the prison system and that almost 50% of the crimes involved are alcohol related. He discussed the use of police action to enforce community instigated prohibitions on alcohol, also reminding us that such action must not be too severe and must have community support (eg. no �commando� operations). The overall thesis proposed by Weatherburn was that we need to address alcohol and drugs more seriously as being causal in indigenous detention - and dedicate more resources to specific drug/alcohol interventions - given that the significant investments in addressing the broader social and economic circumstances had not reduced harms associated with indigenous imprisonment to date.

Dr Mark Wenitong spoke about his Aboriginal Woochopperan Health Centre in Cairns, concerning delivery of smoking cessation and other services to both local and remote communities. He reiterated us of the high rates of smoking and drinking as well as the costs. Domestic violence and injuries can result in an air ambulance evacuation and long term hospitalisation, quite apart from the uncostable social disruption for families involved.

Following the opening plenaries there were another 7 sessions on a variety of subjects including detoxification, SMART recovery, prison issues, cannabis (including a trial from Sydney of using lithium) and the so-called heroin drought.

In one session, we were told that 50% of young people in a particular birth cohort had used cannabis and 22% had reported a cannabis use disorder at some time. I found this figure very high and wondered about the definition. We were also told that �The evidence suggests that most young people who use cannabis do so infrequently and that they do not develop a cannabis use disorder�. There were other presentations concerning psychosis and cannabis use, inhalant use and hepatitis C.

These afternoon sessions were all delayed slightly by the running of the Melbourne Cup. We heard in a brief presentation from Professor John Strang of London that the standard of methadone prescribing in England improved in the ten years during which his �Orange� guidelines were circulated to GPs (1999). Findings from comparable surveys in 1995 and 2005 showed a modest increase from around 45mg daily dose to 54mg. This is still a long way from the ideal, believed to be between 80 and 100mg daily. Strang�s own guidelines recommend a minimum effective daily dose of 60mg. In response to my question after the session, he explained findings of 37mg daily in another UK study he performed in 2005 used different methodology so he did not bring it up at the presentation. He agreed with me that the state of clinical standards in the UK were �disastrous�, but �less disastrous than they had been in 1995�.

Professor Strang told us that dose supervision was now more common in England and there was less methadone ampoule and tablet prescribing This may be a good thing overall, yet it is also possible that such treatment suited some patients who may do poorly on standard oral treatment. Along that line, he reported a new initiative prescribing heroin and methadone ampoules to addicts who had failed other forms of treatment in London, Brighton and two other centres in England. They are using the same protocols as the Swiss trials started in 1995.

Strang�s London colleauge, Dr Soraya Mayet spoke about QT intervals being affected by methadone, especially at high dose. She had the whole room debating how often cardiographs should be done, yet an authority on the subject wrote in Lancet recently that routine cardiographs are unnecessary in new patients joining treatment (Krantz 2005). In fact, most reported symptomatic cases either had other risk factors such as cocaine use or else they were on extremely high doses (mean 300mg daily) and/or were pain management patients.

Our own group presented analysis of trough blood R-methadone levels showing that these were lower (1) in high dose patients and (2) in those smoking cannabis, but that there was no significant association with benzodiazepines or alcohol using stepwise regression analysis of 70 cases uncomplicated by other medication use. Causation would have to be determined by further research.

Eight parallel sessions followed afternoon tea, covering worker burnout, injecting rooms, blood borne viruses, tobacco interventions in mental patients, pregnancy and indigenous communities with an optional visit to the Wuchopperen Health Service in Cairns where inhalant use is being addressed.

The conference dinner was a noisy but pleasant affair at the Pacific International ballroom. Everyone seemed to mix and let their hair down. I looked at my watch as security hounded us out - it was midnight!

Comments by Andrew Byrne ..

References:

Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368;9535;556-557

Cairns APSAD Conference 2006 summary: day one

APSAD Annual Scientific Conference. Cairns, Queensland.

Mon 6th November 2006.

The morning started with Christopher Pyne MP, parliamentary secretary to the Minister for Health and Ageing, giving a spirited talk on the public health benefits of alcohol restrictions.

The convenors cleverly commenced with plenary presentations on the least and most dangerous drugs back-to-back with national and international expert speakers.

Frank Vocci from the American NIDA (NIH) spoke about mooted pharmacotherapies for cannabis addiction. He quoted figures for �ever used� and recently used, finding that about 50% of all Americans have exposure to the drug. We were told that many of the subjects in treatment trials in the US are young people who are referred from the court system as an alternative to jail. He broached possible novel approaches such as the cannabinoid agonists as well as the French antagonist, rimonabant. Other possibilities are lithium, antidepressants or other drugs to counter withdrawal symptoms as well as reduce cravings in dependent subjects. In questioning our speaker later, I was told that while naltrexone showed some promise in rodent studies, that in humans, the drug seemed to augment the effect of cannabis, a very worrying finding. It may paradoxically be a benefit if smokers can get as �high� by smoking half as much. It would appear that this finding alone has been sufficient to stop further funding of such research by NIH.

I also noted with Dr Vocci that the US buprenorphine post-marketing survey released recently showed that over a third of new patients see no doctor, psychologist, pharmacist, nurse or other health care worker in the first 30 days after their initial prescription for the drug in dependency treatment. Unsupervised maintenance treatment is a paradigm shift indeed. It is not evidence based, yet it is being encouraged by health authorities and professional bodies here and overseas for some reason. At present it must be considered a noble experiment.

Smoking and nicotine dependence was covered next by Professor Wayne Hall from Brisbane. In a logically structured talk he broached the novel area of genetic studies to determine susceptibility to addiction to nicotine and/or available treatment. He quoted some moves to look at �vaccinating� children where appropriate risks were high, yet we were told of major ethical concerns here. While he said that parents would always have the right (and responsibility) to choose, he would not advise such moves under any foreseeable circumstances. At the very end of his talk he reminded us of the use of �snus� oral tobacco in Sweden and its potential for harm reduction (which seems to have been ignored across the world, despite promise of reduced harms).

The strict anti-smoking laws in Queensland required that the few smokers present had to stand in a small roped off area near the convention centre drive-way. Not very dignified, but that�s the law. Luncheon included some delicious crumbed reef fish but the rest of the fare was middling to ordinaire.

No less than seven parallel sessions followed. Alcohol in indigenous communities, dual diagnosis, Europe�s highest overdose rates in the UK being addressed with pilot study of naloxone provision, hepatitis referrals and treatment successes in Sydney as well as monitoring of drug trends in Australia and America.

It seemed incongruous that the Turning Point group from Melbourne presented an integrated system of assessment and treatment for hepatitis C within the clinic. Yet this model would have little use in Victoria which depends almost completely on GPs and pharmacies for pharmacotherapies unlike New South Wales which has a large proportion in clinic settings. Their excellent model should be replicated in some form in each and every such clinic in the interests of public health.

Next we presented our own practice approach using community prescribing and a shared care model with liver clinic referrals, which might just be ideal for Victoria! We found that 75% of Redfern injectors were Hep C positive and 75% of those patients had chronic hepatitis, half of whom had high risk factors for cirrhosis. Out of 250 patients seen over a 3 year period at the practice, 70 were at risk, 50 were referred to a hepatitis shared-care service and 40 attended. To date about 25 have commenced interferon and ribavirin treatment, mostly with excellent responses and modest to moderate side effects. Of 29 biopsies performed, 24 showed at least moderate fibrosis, consistent with recent advice to allow treatment to proceed without a requirement to do liver biopsy.

Louisa Degenhardt gave a learned and teasingly titled plenary talk entitled: �Are we the biggest users of ecstasy in the world, and how worried should we be if we are?� She pointed out that �biggest� could mean greatest overall amount consumed per person, but it could equally mean more frequent, youngest or longest career of drug use. She emphasised the dangers of ecstasy but put them into perspective with regard to the large proportion of young people who use the drug regularly, often with few apparent adverse effects and low mortality compared with heroin, cocaine, tobacco and alcohol.

We were asked to allow a bigger input of consumers in opioid maintenance delivery as now standard practice in other areas of health care. Annie Madden and Joanne Bryant urged mangers to take heed of the needs of addicts in treatment and involving them in decisions affecting them. My own feeling is that until there is wider choice and a little competition, the present stigmatising and monopolistic system will remain in place.

We then had an interesting talk from Ann Roche on the Australian workforce in dependency and how only ~75% are happy and satisfied with their jobs. I would have thought that is better job satisfaction than many other trades or professions. By contrast in America, McLellan and Keber found quite the opposite with unhappy workers, �burnout� and short careers in the dependency treatment field. (McLellan AT, Carise D, Kleber HD. Can the national addiction treatment infrastructure support the public's demand for quality care? J Subs Abuse Treat 2003 25:117-121).

Next there were seven more parallel break-out sessions in which mental health, alcohol in the workplace, NGO�s, heroin dependency in pregnancy, state comparisons of methadone treatment and indigenous dependency research partnerships were all covered. There were many useful �messages� such as NGO�s being undervalued in doing work which governments cannot or will not do. We were told that some women avoided methadone in pregnancy for fear of addicting their baby to drugs, despite on-going and very harmful illicit drugs use. Victoria has not solved the problem of diverted drugs by severe restrictions on take-away medication (indeed, they have just freed up access to dispensed drugs for stable patients).

Cairns is a special place and the timing was perfect as a full moon rose on the first night, visible from the entire boardwalk waterfront. The temperature was around 29 degrees for the three days and while there was a slight heat haze, there were no tropical storms, earthquakes nor tsunamis. The silky oaks, bougainvillea and flamboyant trees were in full flower while numerous fragrant tropical species, frangipani, palms, grasses and even mangroves graced the place in abundance.

Comments by Andrew Byrne ..

Memory - impact (or lack of it) from ecstasy use.

Simon NG, Mattick RP. The impact of regular ecstasy use on memory function.
Addiction 2002 97:1523-29

This interesting study compared regular ecstasy users with cannabis users on
a variety of verbal, spacial and other tests of memory. It is gratifying to
see a realistic comparison after numerous studies, mostly from America, in
which drug users are compared with teetotallers.

Most of the ecstasy using volunteers (average lifetime use ~90 tablets) were
also cannabis users, making the comparison particularly appropriate and the
results therefore more rigorous.

"Conclusion: This study does not show memory impairment in a group of
ecstasy users relative to cannabis using controls. The previously reported
association of life-time exposure to ecstasy and memory was not found. The
findings may indicate a confounding role of cannabis use, as has been
recently reported."

comments by Andrew Byrne ..

Opioid Maintenance: Back to Basics. Therapeutic lessons from Vioxx and LAAM.

Concord Dependency Seminar: Tuesday September 26th 2006

Presenters: Dr Andrew Byrne, Redfern, NSW. Professor Ernie Drucker, USA.

This seminar provided an overview of opioid use and treatment issues, including patterns of drug use, scientific research and treatment decisions that must be made within the context of the consultation. There was also an overview of topical issues surrounding amphetamine use. In the introduction to this evening, we were reminded that combination buprenorphine has given us one more option for management of opioid dependence and is thus an important addition to treatment possibilities. In the general sense, we should approach prescribing for addiction disorders in the same manner as prescribing for any other medical condition. If we prescribe according to clinical guidelines we will get predictable outcomes, and likewise when we step outside such guidelines as for unusual cases, we should ensure careful documentation and sometimes a second opinion. We should attempt to tease out the evidence based aspects of treatment versus what we do which is non-evidence based. Most therapeutic regimes probably contain elements of both. We should take care to define the problem clearly with the correct diagnosis, and then use a consistent approach to therapeutics.

A fairly typical case history was shown to us, followed by a possible treatment approach and analysis of what was or was not evidence based.

• 30 year old male with a 7 year history of heroin use, now relapsed.


• Works as a part-time cook, smokes 20/day and does not drink any alcohol.


• Only had brief episodes off heroin, eg whilst in jail.


• Hep C positive, HIV negative, urinalysis positive for morphine.

An approach to initial treatment might include the following:

• Give counselling re HIV/HCV infection.


• Arrange urine and blood tests.


• Initiate MMT - starting dose 30-40mg.


• Discuss teeth, halitosis, diet.


• Arrange next appointment for 4 - 7 days later.

We were asked to consider which of these treatment decisions are research based, and which are "sound medical practice". This led on to an overview of scientific research methods in medicine and a reminder of the various forms that they can take. Whilst observational reports do not constitute "Level A" evidence, it was exactly this type of research which first supported methadone maintenance as a treatment. "Negative" evidence (an absence of reported ill effects) is cited to support methadone and, increasingly buprenorphine treatment in pregnancy. We can consult the Cochrane summaries, look for cohort studies and individual randomised controlled trials as well.

Professor Drucker then spoke about substitution treatments for amphetamine use and parallels with opiates. He told us that the scientific research on amphetamine replacement therapy is now at the same place as studies were with regards to early use of methadone maintenance therapy. There was a show of hands from the audience to indicate that most people had noticed an increased use of amphetamines in their area in the last 5 years. This has been linked to the heroin drought, which has also seen the arrival of Ice in Australia. The drought has been determined by markets and it was noted that if the market is there, the drug will appear. In both England and Europe stimulant use is now far more common than heroin use. The ease with which amphetamines can be made, (they don't have to be grown or refined), predicts an infinite stream of stimulant supplies. As with any addictive substance, there are different patterns of stimulant use, which include a stable controlled use and a more pathological pattern, particularly when amphetamines are combined with Viagra. About 20% of people who use stimulants exhibit a problematic pattern to their use and both amphetamine and �crack� users often seek help sooner than people who use other drugs, sometimes within 6 months of commencing amphetamines or cocaine (for opiates it is 2-4 years typically).

Studies in the 1980s showed there was a negligible HIV incidence among amphetamine users. In the same decade, 4 studies in the BMJ showed that oral amphetamines decreased the intravenous use of amphetamines in those who were addicted. Advantages to oral treatment also included health professionals being able to regularly review the patient, being able to titrate the dose of stimulant, and the patient receiving a drug whose composition was known. Since then, a further 20 or more studies have shown that oral stimulant replacement therapy has reasonable treatment retention rates and a reduction in adverse outcomes, where government policy in Australia has not improved the outlook for amphetamine users at all.

A number of studies have looked at the role of anti-depressants for amphetamine withdrawal and there is currently no evidence to suggest that anti-depressants help. Professor Drucker emphasised the increased danger of combining stimulant use with Viagra use, citing the increased prevalence of HIV in the New York gay community. He pointed out that amphetamine users are desperate to avoid the "crash" as the stimulant effects wear off, and so a sustained release substitution treatment would make good pharmacological sense. The use of stimulants has very deep roots in many different cultures, including medical students cramming for exams and truck drivers on long runs. In Jamaica, people who worked on the land doing hard labour for long hours at a stretch showed a significant level of stimulant use so it can be seen that societal expectations and conditions linked to people's rights should be considered as a necessary part of the solution to increased stimulant use.

Professor Drucker pointed out the irony of the USA having a record number of children now diagnosed with ADHD and currently on stimulants (Ritalin and dexamphetamine) as treatments. This is in a country where it is the Drug Enforcement Agency (DEA) that gives the licences to prescribe opiates and where it is the police who give the drug education in schools. Medical authorities have little say in this, despite being the clinicians called upon when things go wrong. There is evidence that some of those in treatment for ADHD are selling their medication in an amphetamine-hungry market.


In Australia (unlike England) we cannot currently prescribe amphetamines as a replacement therapy, so what do we do? The following were offered as guidelines:

• be supportive in a non-judgmental way


• remember that many people use drugs for a while and then stop


• treat all co-morbid problems


• offer brief harm reduction interventions eg. sniff/smoke, don't inject


• always see if there is a safer way of using and/or a longer acting form of the drug

The question arose as to whether the principles outlined in the discussion on amphetamine replacement therapy can be applied to benzodiazepine (BZD) use. It is likely that uncontrolled prescribing of BZD by doctors (in large amounts and with no supervision or counselling) is part of the problem in Australia. Valium is available as a PBS item in quantities of fifty tablets, and whilst the Doctor Shopping Hotline is a useful service for tracking �overusers� it has significant limitations. Limitations include the fact that it doesn't include private prescriptions of BZD, and in a 3 month period will show that a patient has seen 6 or more prescribers of BZD or has received greater than a certain number of scripts. People can have a significant problem with BZD use when using amounts less than this. There was a discussion about experiences of controlled BZD prescribing for BZD addiction and it was acknowledged that it is very labour intensive for the pharmacists who often don't charge for the daily pickup of BZDs by the patient.


The next part of this seminar dealt with some of the particulars of opioid replacement therapy and Dr Byrne began by discussing induction onto MMT. Whilst there are some differences in terms of the rate of increases in methadone doses, people are generally started on between 30 and 40mg of methadone. We should be guided by the patient's circumstances as to whether to commence them on methadone or buprenorphine. Whilst research seems to indicate that dose reductions are almost never indicated, we must understand the best way to approach this if a patient requests to "come down". The traditional indicators of stability (including good psychosocial functioning, stable housing, relationships going OK, no current problematic drug use) should be present before decreasing the dose of opioid replacement. There was some discussion of time frames and it was generally agreed that a minimum of 3 months of stability was advisable. Whilst there are no hard and fast rules, it was also suggested by one experienced member of the audience that a patient should probably be out of jail for a minimum of 2 years, as the recidivism rate within the 2 year period is high. Doses should be reduced in small steps (eg. no more than 10% in 3-4 weeks), gradually (the increments of reduction should get smaller the lower the dose becomes), and with a constant lookout for any indicators of instability. With general principals of pharmacotherapy in mind, the aim is to achieve the minimum effective dose. Dr Byrne suggested that no-one should stay on MMT for greater than 1 year without seriously considering a dose reduction. It was recognized that some patients will require replacement opioids for life while a majority of �starters� will successfully withdraw from maintenance treatment.

Reductions down to 40mg of methadone allow a transfer from methadone onto buprenorphine, and it was pointed out that patients can be very grateful for the opening up of this possibility. Patients on very low doses of methadone (say, 20mg), are at risk of overdosing as their tolerance to opiates lessens, so reversion back to illicit opiate use can be particularly dangerous for those on small doses of methadone. With regards to take-away opioid replacement therapy, there is very little research as to whether supervision of doses is useful, though it is generally agreed that some supervision is needed- finding the ideal amount for the patient is the task.

One study in the USA (Rhoades et al. AJPH) did show significant benefits for patients receiving increased take-away ORT (5 vs. 2 per week). Boundaries however must be set, never doing "favours" for particular patients but maintaining consistency with some flexibility.
Frequency of consultations depend on stability of both dose and the patient's life circumstances. The rule of thumb is see the patient often during inductions, then less often when the patient is stable (eg once a month). Dr Byrne told us that about half of his patients attend every fortnight for a medical consultation.

The role of counselling in these situations has been questioned. One old study by Jaffe showed that in two groups of patients both on MMT, one receiving no counselling and social supports, and the other receiving a large amount of counselling and social supports, there was little or no difference in outcomes for the patients. This has been replicated in other studies, but it was pointed out that just giving the methadone with �bare-bones� medical assessments still has a significant �personal� therapeutic input, quite apart from the drug administration. This seems to suggest that by far the most important aspect of clinical care is placing people on supervised opioid replacement therapy. Similarly, there is little evidence to support urinary drug screens in terms of improved outcomes for patients, though UDS have been traditionally done since the very first MMT in 1965. It was generally agreed that UDS do not discourage drug use, yet they are certainly the best indicator of treatment effectiveness both in the individual and across the clinic population.


This seminar ended with a reminder that methadone and buprenorphine are equally effective treatments for opioid dependency. Dr Byrne took us back to Osler's maxims as a reminder of what constitutes good clinical care, whether it be for patients with opioid dependence or otherwise.

• "Let me take the history.


• Let the medical student perform the physical exam,


• Throw the lab results away,


• And I'll give you the diagnosis."

And.....

• "To study the phenomena of disease without books is to sail on uncharted sea, while to study books without [seeing] patients is not to go to sea at all."

Summary written by Dr Jenny James, Daruk AMS.

References:

Senay EC, Jaffe JH, diMenza S, Renault PF. A 48-week study of methadone, methadyl acetate, and minimal services. In: Fisher S. and Freedman AM, eds, Opiate Dependence: Origins and Treatment. New York: Halsted 1973 185-201
Schwartz RP, Highfield DA, Jaffe JH, et al. A Randomized Controlled Trial of Interim Methadone Maintenance. Arch Gen Psychiatry 2006 63:102-109
Yancovitz SR, Des Jarlais DC, Peyser NP, Drew E, Friedmann P, Trigg HL, Robinson JW. A randomised trial of an interim methadone maintenance clinic. (1991) American Journal of Public Health 81:1185-91
Rhoades HM, Creson D, Elk R, Schmitz J, Grabowski J. Retention, HIV Risk, and Illicit Drug Use during Treatment: Methadone Dose and Visit Frequency. 1998 Am J Public Health 88:34-39